P1085: HISTOLOGICAL TRANSFORMATION OF FOLLICULAR LYMPHOMA TO DIFFUSE LARGE B-CELL LYMPHOMA WITHIN 48 MONTHS (TOD48) INDICATING AN ADVERSE PROGNOSIS: EVIDENCE FROM TWO POPULATION-BASED COHORTS
Authors: LI Zihua, Minyue Zhang, Jian Hou, Hong-Hui Huang
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Histological transformation (HT) is a devastating event that could alter the indolent nature of follicular lymphoma (FL). Aims: Based on a population-based approach, this retrospective study aimed to investigate the impact of the early transformation of FL to diffuse large B-cell lymphoma (DLBCL) on clinical outcomes and prognoses of patients. Methods: The Surveillance, Epidemiology, and End Results (SEER) Incidence -Research Plus Data from 18 Registries (2000 to 2018) was first used to extract the FL cases with DLCBL (tFL) as a secondary diagnosis at least six months after FL diagnosis. The Epanechnikov kernel method was applied to estimate the transformation hazard rate. Furthermore, these results were externally validated in United Kingdom’s Haematological Malignancy Research Network (HMRN) cohort. Results: A total of 1,079 cases of tFL (45.6% of females) were identified and included in the current study. The median time to transformation is 51 months (ranging from 6 to 227). The estimated transformation hazard curve (Fig 1A) depicted a transformation risk peak within 48 months after FL diagnosis. The Kaplan-Meier curve demonstrated that patients who experienced early transformation within 48 months (TOD48) had inferior overall survivals compared with those with non-TOD48 (median OS: 68 versus 182 months, P<0.0001) (Fig 1B). Univariate and multivariate logistic analysis revealed that age at FL diagnosis > 75 years and B symptoms were significantly associated with TOD48 (P<0.05). In the HMRN validation cohorts, there were 96 cases of tFL, among which 26 cases had both FL and paired transformed DLBCL samples for detecting gene mutation profiles. The transformation hazard curve regenerated from the HMRN cohort displayed a similar pattern to those of the SEER cohort. The Kaplan-Meier curve also showed that patients with TOD48 have poorer overall survivals than those with non-TOD48 (median OS: 59.9 months versus 135.4 months, P<0.0001) (Fig 1C). The Cox regression indicated that TOD48 was associated with adverse prognosis (HR: 3.121, 95% CI: 1.784-5.459, P=0.000). The risk effect remained after adjustment by FLIPI1 scores and treatment approaches (adjusted HR: 3.120, 95% CI: 1.707-5.704, P=0.000). The logistic analysis determined that POD24 significantly predicted TOD48 (OR: 5.029, 95% CI: 1.264-20.002, P=0.022). When examining DLBCL mutation data (n=26), univariate logistic regression identified a significant relationship between SGK1 mutation and non-TOD48 transformed DLBCL (OR: 0.107, 95% CI: 0.015-0.770, P=0.026). Summary/Conclusion: This retrospective population-based study revealed that TOD48 was an independent risk factor for the adverse prognosis in tFL patients for the first time. Age at FL diagnosis > 75 years, and B symptoms were susceptible to the early histological transformation of FL to DLBCL. More attention should be paid to those patients in future prospective clinical trials.Keywords: Population, Transformation, Prognosis, Follicular lymphoma